Aleksandra Rojek1, Maciej Flader2, Elzbieta Malecka2, Marek Niedziela3. 1. Poznan University of Medical Sciences, 2nd Chair of Pediatrics, Department of Pediatric Endocrinology and Rheumatology, Molecular Endocrinology Laboratory, Poznan, Poland. 2. Karol Jonscher's Clinical Hospital of Poznan University of Medical Sciences, Department of Pediatric Endocrinology and Rheumatology, Poznan, Poland. 3. Poznan University of Medical Sciences, 2nd Chair of Pediatrics, Department of Pediatric Endocrinology and Rheumatology, Molecular Endocrinology Laboratory, Karol Jonscher's Clinical Hospital of Poznan University of Medical Sciences, Department of Pediatric Endocrinology and Rheumatology, Poznan, Poland.
Abstract
OBJECTIVE: X-linked Adrenal Hypoplasia Congenita (AHC) is a rare disorder caused by mutations in NR0B1 (DAX1) gene. DESIGN: We present two boys (cousins) with AHC who came to our attention at the age of 10 days and 15 days, respectively, in a life-threatening state. Laboratory studies in their neonatal periods showed hyponatremia and hyperkalemia. Primary adrenal insufficiency was confirmed, with severely low serum cortisol levels and high plasma ACTH levels. Hydrocortisone therapy with additional saline and glucose infusions were started immediately. Two exons of the NR0B1 (DAX1) gene were amplified using PCR and directly sequenced. RESULTS: Molecular analysis of the NR0B1 (DAX1) gene revealed a novel mutation, c.315G>A (p.W105X) in exon 1, resulting in the formation of a premature stop codon. Further studies showed that mothers, the maternal grandmother and two of six maternal great aunts were heterozygotes for the mutation. However, the mutation was absent in the maternal great-grandmother. CONCLUSIONS: We show that NR0B1 (DAX1) gene analysis is of great importance for the confirmation of the clinical diagnosis of AHC and highlights the role of genetic counseling for families of AHC patients. The absence of a somatic mutation in the great-grandmother suggests gonadal mosaicism as the mechanism for transmission of the NR0B1 (DAX1) mutation in this family.
OBJECTIVE:X-linked Adrenal Hypoplasia Congenita (AHC) is a rare disorder caused by mutations in NR0B1 (DAX1) gene. DESIGN: We present two boys (cousins) with AHC who came to our attention at the age of 10 days and 15 days, respectively, in a life-threatening state. Laboratory studies in their neonatal periods showed hyponatremia and hyperkalemia. Primary adrenal insufficiency was confirmed, with severely low serum cortisol levels and high plasma ACTH levels. Hydrocortisone therapy with additional saline and glucose infusions were started immediately. Two exons of the NR0B1 (DAX1) gene were amplified using PCR and directly sequenced. RESULTS: Molecular analysis of the NR0B1 (DAX1) gene revealed a novel mutation, c.315G>A (p.W105X) in exon 1, resulting in the formation of a premature stop codon. Further studies showed that mothers, the maternal grandmother and two of six maternal great aunts were heterozygotes for the mutation. However, the mutation was absent in the maternal great-grandmother. CONCLUSIONS: We show that NR0B1 (DAX1) gene analysis is of great importance for the confirmation of the clinical diagnosis of AHC and highlights the role of genetic counseling for families of AHCpatients. The absence of a somatic mutation in the great-grandmother suggests gonadal mosaicism as the mechanism for transmission of the NR0B1 (DAX1) mutation in this family.
Authors: Aleksandra Rojek; Maciej R Krawczynski; Aleksander Jamsheer; Anna Sowinska-Seidler; Barbara Iwaniszewska; Ewa Malunowicz; Marek Niedziela Journal: Int J Endocrinol Date: 2016-08-30 Impact factor: 3.257